Solution Model of the Intrinsically Disordered Polyglutamine Tract-Binding Protein-1

• Published in: Biophysical journal Vol. 102; no. 7; pp. 1608 - 1616
• Main Authors: Rees, Martin, Gorba, Christian, de Chiara, Cesira, Bui, Tam T.T., Garcia-Maya, Mitla, Drake, Alex F., Okazawa, Hitoshi, Pastore, Annalisa, Svergun, Dmitri, Chen, Yu Wai
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.04.2012; Biophysical Society; The Biophysical Society
• Subjects: Binding sites; DNA-directed RNA polymerase; glutamine; Models, Molecular; Molecular structure; Mutation; Nuclear Proteins - chemistry; Protein; Protein Conformation; Proteins; RNA polymerase; Scattering, Small Angle; Solutions; spliceosomes; transcription (genetics); X-radiation; X-Ray Diffraction
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/j.bpj.2012.02.047

Polyglutamine tract-binding protein-1 (PQBP-1) is a 265-residue nuclear protein that is involved in transcriptional regulation. In addition to its role in the molecular pathology of the polyglutamine expansion diseases, mutations of the protein are associated with X-linked mental retardation. PQBP-1 binds specifically to glutamine repeat sequences and proline-rich regions, and interacts with RNA polymerase II and the spliceosomal protein U5-15kD. In this work, we obtained a biophysical characterization of this protein by employing complementary structural methods. PQBP-1 is shown to be a moderately compact but largely disordered molecule with an elongated shape, having a Stokes radius of 3.7 nm and a maximum molecular dimension of 13 nm. The protein is monomeric in solution, has residual β-structure, and is in a premolten globule state that is unaffected by natural osmolytes. Using small-angle x-ray scattering data, we were able to generate a low-resolution, three-dimensional model of PQBP-1.